Erythropoietin-dependent transformation of myelodysplastic syndrome to acute monoblastic leukemia

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3492-3494 ◽  
Author(s):  
Udomsak Bunworasate ◽  
Hilal Arnouk ◽  
Hans Minderman ◽  
Kieran L. O'Loughlin ◽  
Sheila N. J. Sait ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Bone Marrow Cells ◽  
Tritiated Thymidine ◽  
Flow Cytometric Analysis ◽  
Refractory Anemia ◽  
Laboratory Findings ◽  
Flow Cytometric ◽  
Acute Monoblastic Leukemia ◽  
Leukemia Cutis ◽  
Marrow Cells

Abstract Acute monoblastic leukemia (acute myeloid leukemia [AML], French-American-British type M5a) with leukemia cutis developed in a patient 6 weeks after the initiation of erythropoietin (EPO) therapy for refractory anemia with ringed sideroblasts. AML disappeared from both marrow and skin after the discontinuation of EPO. Multiparameter flow cytometric analysis of bone marrow cells demonstrated coexpression of the EPO receptor with CD45 and CD13 on the surface of blasts. The incubation of marrow cells with EPO, compared to without, resulted in 1.3- and 1.6-fold increases, respectively, in tritiated thymidine incorporation and bromodeoxyuridine incorporation into CD13+ cells. Clinical and laboratory findings were consistent with the EPO-dependent transformation of myelodysplastic syndrome (MDS) to AML. It is concluded that leukemic transformation in patients with MDS treated with EPO may be EPO-dependent and that management should consist of the discontinuation of EPO followed by observation, if clinically feasible.

scholarly journals Flow cytometric analysis of the DNA content of bovine and human bone marrow cells

2000 ◽  
Vol 22 (2) ◽  
pp. 117-120
Author(s):  
D. Hoeben ◽  
C. Burvenich ◽  
M. Lenjou ◽  
G. Nijs ◽  
A.‐M. Massart‐Leëan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Content ◽  
Bone Marrow Cells ◽  
Flow Cytometric Analysis ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Flow Cytometric ◽  
Marrow Cells

T(1;7) in Acute Myeloblastic Leukemia following Myelodysplastic Syndrome (RAEB-T)

1988 ◽  
Vol 74 (5) ◽  
pp. 555-558 ◽  
Author(s):  
Raffaella Defferrari ◽  
Mario Sessarego ◽  
Gino Santini ◽  
Franco Ajmar
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Cells ◽  
Acute Myeloblastic Leukemia ◽  
Chromosome 7 ◽  
Chromosome 1 ◽  
Refractory Anemia ◽  
Unbalanced Translocation ◽  
Marrow Cells

A case is described of myelodysplastic syndrome (MDS) refractory anemia type with an excess of blasts in transformation with early leukemic evolution (AML-M1). All bone marrow cells examined showed an unbalanced translocation t(1;7). The karyotype was 45, xy, –21, –7, + der dic t(1;7) (q12;q21). There are reports in the literature of the translocation t(l;7) (pll;pll), which leads to trisomy of the long arms of chromosome # 1 and monosomy of the long arms of chromosome # 7. In the case here described the breakpoints of the chromosomes involved in the translocation differ from the classic ones: in this case there is trisomy of the region 1q12→1qter and monosomy of the region 7q21→7qter. Some clinical and cytogenetic considerations are suggested.

scholarly journals Chronic myelodysplastic syndrome (preleukemia) with the Philadelphia chromosome

Blood ◽  
1980 ◽  
Vol 56 (2) ◽  
pp. 262-264 ◽  
Author(s):  
DG Roth ◽  
CM Richman ◽  
JD Rowley
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Cells ◽  
Philadelphia Chromosome ◽  
Laboratory Findings ◽  
Chronic Granulocytic Leukemia ◽  
Hematologic Disorder ◽  
Erythroid Hyperplasia ◽  
Granulocytic Colony

Abstract A patient with severe anemia, reticulocytopenia, and erythroid hyperplasia of the bone marrow developed fatal acute nonlymphocytic leukemia after 3 yr. A Philadelphia chromosome with the typical 9/22 translocation t(9q +;22q-) was identified by banding techniques in a small number of bone marrow cells throughout the preleukemic phase of the illness (14%--38% of metaphases) and during the acute transformation (50%). Granulocytic colony formation in vitro was abnormal in the preleukemic phase. The diagnosis of chronic granulocytic leukemia was excluded on the basis of clinical and laboratory findings. The identification of the Ph1 chromosome in this form of chronic myelodysplastic syndrome (preleukemia) provides a new example of a hematologic disorder predisposing to acute leukemia in which this chromosomal abnormality occurs.

scholarly journals Altered oncoprotein expression and apoptosis in myelodysplastic syndrome marrow cells

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4275-4287 ◽  
Author(s):  
R Rajapaksa ◽  
N Ginzton ◽  
LS Rott ◽  
PL Greenberg
Keyword(s):  
Myelodysplastic Syndrome ◽  
Cell Survival ◽  
Marrow Cell ◽  
Leukemic Cell ◽  
Refractory Anemia ◽  
Maturation Stage ◽  
Mean Values ◽  
Cd34 Cells ◽  
Marrow Cells

Abstract Ineffective hematopoiesis with associated cytopenias and potential evolution to acute myeloid leukemia (AML) characterize patients with myelodysplastic syndrome (MDS). We evaluated levels of apoptosis and of apoptosis-related oncoproteins (c-Myc, which enhances, and Bcl-2, which diminishes apoptosis) expressed within CD34+ and CD34- marrow cell populations of MDS patients (n = 24) to determine their potential roles in the abnormal hematopoiesis of this disorder. Marrow cells were permeabilized and CD34+ and CD34- cells were separately analyzed by FACS to detect: (1) a subdiploid (sub-G1) DNA population, and (2) expression of Bcl-2 and c-Myc oncoproteins. Within the CD34+ subset, a significantly increased percentage of cells demonstrated apoptotic/sub- G1 DNA content in early (ie. refractory anemia) MDS patients compared with normal individuals and AML patients (mean values: 9.1% > 2.1% > 1.2%). Correlated with these findings, the ratio of expression of c-Myc to Bcl-2 oncoproteins among CD34+ cells was significantly increased for MDS patients compared to those from normal and AML individuals (mean values: 1.6 > 1.2 > 0.9). Bcl-2 and c-Myc oncoprotein levels were maturation stage-dependent, with high levels expressed within CD34+ marrow cells, decreasing markedly with myeloid maturation. Treatment of seven MDS patients with the cytokines granulocyte colony-stimulating factor plus erythropoietin was associated with decreased levels of apoptosis within CD34+ marrow cells and may contribute to the enhanced hematopoiesis in vivo that was shown. These findings are consistent with the hypothesis that altered balance between cell-death (eg, c-Myc) and cell-survival (eg, Bcl-2) programs were associated with the increased degrees of apoptosis present in MDS hematopoietic precursors and may contribute to the ineffective hematopoiesis in this disorder, in contrast to decreased apoptosis and enhanced leukemic cell survival in AML.

scholarly journals Simultaneous flow cytometric DNA and volume measurements of bone marrow cells as sensitive indicator of abnormal proliferation patterns in rat leukemias.

1979 ◽  
Vol 27 (1) ◽  
pp. 398-403 ◽  
Author(s):  
G Valet ◽  
B Fischer ◽  
A Sundergeld ◽  
G Hanser ◽  
V Kachel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Parameter Analysis ◽  
Alpha Cell ◽  
Brown Norway ◽  
Normal Limits ◽  
Flow Cytometric ◽  
Volume Measurements ◽  
Marrow Cells

Simultaneous flow cytometric DNA and volume analysis of normal rat bone marrow cells shows three populations of nucleated cells with different mean volume. Each of these populations proliferates in a distinct cell cycle (alpha, beta, gamma). Normally the alpha-cell cycle has the highest amplitude, the beta-cell cycle is intermediate, and the gamma-cell cycle is low. The alpha-cell cycle was very significantly depressed and the beta + gamma-cell cycle was increased in three different rat leukemias (L5222, Shay, BNML), growing on three different rat strains (BDIX, Holtzmann, Brown Norway). The two parameter analysis further revealed that cells of the beta + gamma-cell cycle were slightly hyperdiploid and hypertetraploid in leukemic animals. The decrease of the alpha-cell cycle and the hyperploidies were more sensitive indicators for the abnormal proliferation pattern than the analysis of one parameter DNA distributions which remained within normal limits in all three leukemias.

NKG2D-Mediated Marrow Injury in Paroxysmal Nocturnal Hemoglobinuria and Its Related Disorders.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3674-3674
Author(s):  
Nobuyoshi Hanaoka ◽  
Tatsuya Kawaguchi ◽  
Kentaro Horikawa ◽  
Shoichi Nagakura ◽  
Sonoko Ishihara ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Cells ◽  
Close Association ◽  
Bone Marrow Failure ◽  
Γδ T Cells ◽  
Refractory Anemia ◽  
Nkg2d Ligands ◽  
Marrow Cells

Abstract Immune mechanism is considered to exert in the pathogenesis of marrow failure in paroxysmal nocturnal hemoglobinuria (PNH), idiopathic aplastic anemia (AA) and myelodysplastic syndromes (MDS); however, the molecular events are unknown. We have currently reported the appearance of NKG2D ligands such as cytomegalovirus glycoprotein UL16 binding proteins (ULBPs) and MHC class I-related chains A and B (MICA/B) on granulocytes and CD34+ marrow cells of some patients with PNH and its related diseases (Hanaoka N, et al. Blood. 2006;107:1184–1191). ULBP and MICA/B are stress-inducible membrane proteins that appear in infection and transformation. The ligands share NKG2D receptor on lymphocytes such as NK, CD8+ T, and γδ T-cells and promote activation of the lymphocytes. Cells expressing the ligands are then deadly injured by NKG2D+ lymphocytes (Groh, PNAS 1996; Cosman, Immunity 2001). Indeed, cells expressing NKG2D ligands were killed in vitro by autologous NKG2D+ lymphocytes of our patients (Hanaoka N, et al. Blood. 2005;106:304a; Blood. 2006;108:295a). In further analysis, ligands were detected on granulocytes in 47 (53%) of 88 patients: 11 (58%) of 19 PNH, 28 (60%) of 47 AA, and 8 (36%) of 22 refractory anemia. Ligands were also detected on immature bone marrow cells in all 11 patients (3 PNH, 5 AA, and 3 refractory anemia) who permitted analysis of their marrow cells. In the patients, it is conceivable that blood cells were exposed to a certain stress to induce NKG2D ligands, leading to NKG2D-mediated marrow injury. We also observed a close association of the ligand expression with pancytopenia and favorable response to immunosuppressive therapy by prospective analysis of 5 patients (3 AA-PNH syndrome and 2 AA) for more than one year up to 5 years. Thus, we here propose that NKG2D-mediated immunity, which drives both NK and T-cells, is critically implicated in the pathogenesis of bone marrow failure of PNH and its related disorders.

Expression of dlk1 in the Bone Marrow Cells of Patients with Myelodysplastic Syndrome and Its Clinical Significance

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5042-5042
Author(s):  
Zonghong Shao ◽  
Lanzhu Yue ◽  
Rong Fu ◽  
Lijuan Li ◽  
Erbao Ruan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Early Diagnosis ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Rt Pcr ◽  
Normal Controls ◽  
Lower Expression ◽  
Bone Marrow Blasts ◽  
Marrow Cells

Abstract Abstract 5042 Objective To investigate the expression of dlk1 gene (delta-like 1) in the bone marrow cells of patients with Myelodysplastic syndrome (MDS), and explore the molecular marker for early diagnosis of MDS. Methods The expression of dlk1 mRNA in the bone marrow cells of cases with MDS, AML and normal controls were measured by RT-PCR, aiming to search for the cytogenetic marker of MDS malignant clone. Results The expression of dlk1 mRNA in bone marrow cells of MDS patients (0.7342±0.3652) was significantly higher than that of normal controls (0.4801±0.1759) (P<0.05), and was significantly positively correlated with the proportion of bone marrow blasts(r=0.467,P<0.05). The expression of dlk1 mRNA significantly increased as the subtype of MDS advanced (P<0.05). Patients with abnormal karyotypes displayed significantly higher expression of dlk1 mRNA (0.9007±0.4334) than those with normal karyotypes (0.6411±0.2630) (P<0.05). Patients with higher expression of dlk1(≥0.8) presented significantly higher malignant clone burden (0.4134±0.3999) than those with lower expression (<0.8) of dlk1 (0.1517±0.3109) (P<0.05). Conclusion dlk1 gene was highly expressed in MDS patients, which increased as the subtype of MDS advanced. The expression of dlk1 mRNA was significantly positively correlated with the proportion of bone marrow blasts. High expression of dlk1 gene suggests high malignant clone burden of MDS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Enrichment and characterization of murine hematopoietic stem cells that express c-kit molecule

Blood ◽  
1991 ◽  
Vol 78 (7) ◽  
pp. 1706-1712 ◽  
Author(s):  
S Okada ◽  
H Nakauchi ◽  
K Nagayoshi ◽  
S Nishikawa ◽  
S Nishikawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Bone Marrow Cells ◽  
Flow Cytometric Analysis ◽  
Tyrosine Kinase Receptor ◽  
Dependent Manner ◽  
Hematopoietic Stem ◽  
Marrow Cells

The proto-oncogene c-kit encodes a transmembrane tyrosine kinase receptor for stem cell factor (SCF). The c-kit/SCF signal is expected to have an important role in hematopoiesis. A monoclonal antibody (ACK- 2) against the murine c-kit molecule was prepared. Flow cytometric analysis showed that the bone marrow cells that expressed the c-kit molecule (approximately 5%) were B220(B)-, TER119(erythroid)-, Thy1negative-low, and WGA+. A small number of Mac-1(macrophage)+ or Gr- 1(granulocyte)+ cells were c-kit-low positive. Colony-forming unit in culture (CFU-C) and day-8 and day-12 CFU-spleen (CFU-S) existed exclusively in the c-kit-positive fraction. About 20% of the Lin(lineage)-c-kit+ cells were rhodamine-123low and this fraction contained more day-12 CFU-S than day-8 CFU-S. On the basis of these findings, murine hematopoietic stem cells were enriched with normal bone marrow cells. One of two and one of four Thy-1lowLin-WGA+c-kit+ cells were CFU-C and CFU-S, respectively. Long-term repopulating ability was investigated using B6/Ly5 congenic mice. Eight and 25 weeks after transplantation of Lin-c-kit+ cells, donor-derived cells were found in the bone marrow, spleen, thymus, and peripheral blood. In peripheral blood, T cells, B cells, and granulocyte-macrophages were derived from donor cells. Injection of ACK-2 into the irradiated mice after bone marrow transplantation decreased the numbers of day-8 and day-12 CFU-S in a dose-dependent manner. Day-8 spleen colony formation was completely suppressed by the injection of 100 micrograms ACK-2, but a small number of day-12 colonies were spared. Our data show that the c- kit molecule is expressed in primitive stem cells and plays an essential role in the early stages of hematopoiesis.

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